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The origin and evolution of human pathogens.

What are the genetic origins of human pathogens? An international group of scientists discussed this topic at a workshop that took place in late October 2004 in Baeza (Spain). Focusing primarily on bacterial pathogens, they examined the role that pathogenicity islands and bacteriophages play on determining the virulence properties that distinguish closely related members of a given species, such as host range and tissue specificity. They also discussed an instance in which closely related bacterial species differ in the production of a cell surface modification mediating resistance to an antibiotic as a result of the disparate regulation of homologous genes. In certain pathogens, genes normally carrying out housekeeping functions may adopt new functions, whereas in other organisms, genes that respond to stresses associated with non-host environments are silenced during infection to prevent the expression of products that interfere with the normal colonization process. The adaptive behaviour of certain pathogens relies on gene variation at certain loci that by virtue of containing polymeric repeats in regulatory or coding regions, can generate variants that may or may not express products that modify the cell surface of the organism. The meeting also addressed the properties of ORFan genes, which have no homologues in the sequence databases, as well as the creation of genes de novo by duplication and divergence.

Bacteria↗

Adsorption and desorption of humic acid on aminated polyacrylonitrile fibers.

Aminated polyacrylonitrile fibers (APANFs) were prepared by surface modification and were used as an adsorbent to remove humic acid from aqueous solutions. The APANFs were found to be very effective in removing humic acid at the pH range from 2 to 10. The adsorption isotherm obeyed both the Langmuir and Freundlich models, and the adsorption kinetics followed an initial diffusion-controlled and then an attachment-controlled adsorption pattern. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy revealed that chemical bonds were formed between the nitrogen atoms in the amine groups on the fibers and humic acid molecules adsorbed, suggesting that, besides electrostatic interaction, surface complexation also played an important role in humic acid adsorption on the APANFs. The humic acid adsorbed on the APANFs can be effectively desorbed in a 0.1 M NaOH solution, and the regenerated APANFs can be reused in the subsequent adsorption cycles without significant loss of the adsorption capacities.

Journal Article↗

Effects of chemical modifications on the surface- and protein-binding properties of the light chain of human high molecular weight kininogen.

The light chain of kallikrein-cleaved human high molecular weight kininogen is solely responsible for its cofactor activity in blood clotting. Sequencing of the NH2-terminal region of the light chain reported herein identified the third kallikrein cleavage site of high molecular weight kininogen as Arg-437. The co-factor activity of high molecular weight kininogen consists of the capacity to bind to negatively charged surfaces and to factor XI or prekallikrein. Chemical modification of the histidines by either photooxidation or ethoxyformic anhydride affected the equivalent of 14-16 of 23 histidines available and resulted in over 90% loss in procoagulant activity. The modified protein had drastically reduced surface- and zinc-binding capacity, but it bound successfully to either factor XI or prekallikrein. In contrast, modification of two carboxyl groups, which led to approximately 80-90% loss of procoagulant activity, seriously compromised protein binding but left surface binding unaffected. All 3 tryptophans were modified at pH 4.0 with N-bromosuccinimide with a 70% reduction in procoagulant activity, but only 1 tryptophan was available for reaction at pH 7.35, resulting in a 50% loss in activity. Tryptophan modification at acidic pH affected protein binding but did not modify surface or zinc binding. Modification of both available tyrosine and 9 of 18 available lysine residues did not have a significant effect on the procoagulant activity of the light chain. These studies indicate that histidines participate in surface binding and that free carboxyl groups and tryptophan side chains are involved in binding of high molecular weight kininogen to other clotting factors.

Amino Acid Sequence↗

Controlled release of heparin from polypyrrole-poly(vinyl alcohol) assembly by electrical stimulation.

A surface modification technique was developed for the covalent immobilization of poly(vinyl alcohol) (PVA)-heparin hydrogel onto electrically conductive polypyrrole (PPY) film with the objective of achieving controlled release of heparin. First, aldehyde groups were introduced onto PPY film through poly(ethylene glycol) monomethacrylate graft copolymerization and subsequent oxidation in acetic anhydride and dimethyl sulfoxide mixture. Then, the prepared PVA-heparin hydrogel was cast onto the PPY film and covalently immobilized to the film through the reaction between the aldehyde groups on the PPY film and the hydroxyl groups of PVA. X-ray photoelectron spectroscopy was used to characterize the surface-modified film after each stage. The strong attachment of the PVA-heparin layer on the PPY film was confirmed by peel test and scanning electron microscopy. The release behavior of heparin from the substrate with and without electrical stimulation was studied and the experimental results showed that the heparin release rate from the prepared substrate using an electric current of 3.5 mA is twofold higher than that without current.

Biocompatible Materials↗

Covalent attachment of phospholipid analogous polymers to modify a polymeric membrane surface: a novel approach.

A novel method for the surface modification of a microporous polypropylene membrane by tethering phospholipid analogous polymers (PAPs) is given, which includes the photoinduced graft polymerization of N,N-dimethylaminoethyl methacrylate (DMAEMA) and the ring-opening reaction of grafted poly-(DMAEMA) with 2-alkyloxy-2-oxo-1,3,2-dioxaphospholanes. Five 2-alkyloxy-2-oxo-1,3,2-dioxaphospholanes, containing octyloxy, dodecyloxy, tetradecyloxy, hexadecyloxy, and octadecyloxy groups in the molecular structure, were used to fabricate the PAP-modified polypropylene membranes. The attenuated total reflectance FT-IR spectra of the original, poly(DMAEMA)-grafted, and PAP-modified membranes confirmed the chemical changes on the membrane surface. Scanning electron microscope pictures showed that, compared with the original membrane, the surface porosities ofpoly(DMAEMA)-grafted and PAP-modified membranes were somewhat reduced. Water contact angles measured by the sessile drop method on PAP-modified membranes were slightly lower than that on the original polypropylene membrane, but higher than those on poly(DMAEMA)-grafted membranes with the exception of octyloxy-containing PAP-modified membranes. However, BSA adsorption experiments indicated that the five PAP-modified membranes had a much better protein-resistant property than the original polypropylene membrane and the poly(DMAEMA)-grafted membranes. For hexadecyloxy- and octadecyloxy-containing PAP-modified membranes, almost no protein adsorption was observed when the grafting degree was above 6 wt %. It was also found that the platelet adhesion was remarkably suppressed on the PAP-modified membranes. All these results demonstrate that the described approach is an effective way to improve the surface biocompatibility for polymeric membranes.

Adsorption↗

The effect of veneering and heat treatment on the flexural strength of Empress 2 ceramics.

OBJECTIVES: The aims of the study were to test and compare the biaxial flexural strength and reliability of Empress 2 ceramics after heat treatment and the addition of the veneering material and to characterise their microstructures. METHODS: Forty disc specimens (2 x 14 mm) and forty disc specimens (1 x 14 mm) were produced by heat pressing in the EP 500 press furnace. Group 1 (2 x 14 mm Empress 2 core) was as heat pressed and group 2 (2 x 14 mm Empress 2 core) was subjected to the recommended firing cycles. Groups 3 and 4 (1 x 14 mm Empress 2 core) were veneered with the dentine material and heat-treated as per group 2. Groups 1, 2 and 3 were lapped to 800 grit silicon carbide paper on the compressive surface only and group 4 on both the compressive and tensile test surfaces. Twenty disc specimens per group were tested using the biaxial flexure test at a crosshead speed of 0.15 mm/min. Specimens were characterised using X-ray diffraction (XRD) and secondary electron imaging (SEM). RESULTS: Mean biaxial flexural strengths (MPa+/-SD) were group 1: 265.5+/-25.7; group 2: 251.3+/-30.2; group 3: 258.6+/-21.4 and group 4: 308.6+/-37.7. There was no statistical difference between groups 1, 2 and 3 (p>0.05), but differences for group 4 (p<0.05). XRD and SEM revealed lithium disilicate and lithium orthophosphate in the Empress 2 core material and an amorphous glass and some evidence of a crystalline phase in the dentine material. CONCLUSIONS; Veneering or heat treatment of Empress 2 ceramics did not significantly affect the mean biaxial flexural strength (p>0.05) or reliability. Surface modification of the Empress 2 core material increased the mean biaxial flexural strength (p<0.05).

Carbon Compounds, Inorganic↗

Interaction of fibroblast cells on poly(lactide-co-glycolide) surface with wettability chemogradient.

Chemogradient surfaces whose properties are changed gradually along the sample length are of particular interest for the basic studies of the interaction between biological species and surfaces since the effect of a selected property can be examined in a single experiment on one surface. A wettability chemogradient on the poly(L-lactide-co-glycolide) (PLGA) films by treating them in air with corona from a knife-type electrode whose power increases gradually along the sample length. The PLGA surfaces oxidized gradually with the increasing corona power, and the wettability chemogradient was created on the surfaces as evidenced by the measurement of water contact angles and electron spectroscopy for chemical analysis. The wettability chemogradient PLGA surfaces prepared were used to investigate the interaction of fibroblast cells in terms of the surface hydrophilicity/hydrophobicity of PLGA surface. The cells adhered and grown on the chemogradient surface along the sample length were counted and observed by scanning electron microscopy. It was observed that the cells were adhered, spread, and grown more onto positions with moderate hydrophilicity of the wettability chemogradient PLGA surface than onto the more hydrophobic or hydrophilic positions. The maximum adhesion and growth of the fibroblast cells appeared at around water contact angle of 55 degrees. It seems that the wettability plays important roles for cell adhesion, orientation, spreading and growth on the PLGA surface. It might be that this surface modification technique can be used for improving the adhesion and growth of cell onto PLGA film and scaffolds, and can be applicable in the area of the tissue engineering.

3T3 Cells↗

Comparison of amperometric biosensors fabricated by palladium sputtering, palladium electrodeposition and Nafion/carbon nanotube casting on screen-printed carbon electrodes.

Different strategies, including palladium electrodeposition (Pd(CV)), Pd sputtering (Pd(S)) and Nafion-solubilized carbon nanotube casting (Nafion/CNT), were used to modify screen-printed carbon electrodes (SPCEs) for the fabrication of amperometric enzyme biosensors. The electrochemical properties of the bare and modified SPCEs and the optimal conditions for surface modification were determined. The electrochemical response of the bare SPCE to H(2)O(2) under the potential of 0.3 V could be improved about 100-fold by Pd modification by electrodeposition or sputtering. By contrast, the electrochemical response of the bare SPCE was enhanced by only about 11-fold by Nafion/CNT casting. Moreover, the Pd(CV)-SPCEs exhibited better reproducibility of electrochemical response (a relative standard deviation (R.S.D.)<6.0%) than freshly prepared Pd(S)-SPCEs (R.S.D.>10%). The glucose biosensor fabricated from Pd-modified electrodes could be stored for up to 108 days without loosing significant activity. The Pd(CV)-SPCE also showed very reliable signal characteristics upon 50 consecutively repeated measurements of ascorbic acid. The electrocatalytic detection of the Pd-SPCE was combined with additional advantages of resistance to surface fouling and hence good stability. In conclusion, this study demonstrated that deposition of Pd thin film on SPCEs by electrodeposition or sputtering provided superior enhancement of electrochemical properties compared to Nafion/CNT-SPCEs. Despite their high electrochemical response, Pd(S)-SPCEs required an activation process to improve stability and Pd(CV)-SPCEs suffered from poor between electrode reproducibility.

Biosensing Techniques↗

[Interaction of silicone oil with various intraocular lenses. A light and scanning electron microscopy study].

BACKGROUND: Silicone oil is increasingly used as an intravitreal tamponade in severe forms of vitreoretinal disorders, also in pseudophakic eyes. In some patients silicone oil was observed to be adherent to the intraocular implant. MATERIAL AND METHODS: To investigate the interaction of silicone oil with IOL-materials and the influence of lipoproteins of the serum on this interaction we used the following in vitro experimental set-up: Sterile IOLs of different IOL-materials (e.g. PMMA, silicone, hydrogel) and surface-modifications (e.g. Pharmacia 809P and 809C, Soflex LI41U, Alcon AcrySof M60BM, Allergan SI-30NB, SI-40NB, Chiron adatomed 90D, C10 and C31UB, MemoryLens U940A, Corneal ISHEMA 66, Storz H60M) were stored in vitro together with silicone oil (1000 centistokes) with and without a fresh serum solution at 37 degrees Celsius. This combination was rotated slowly and mixed thoroughly three times a day. After 3 and 6 months and a standardized special preparation in an ultrasound bath and air treatment, the IOLs were examined by light microscopy followed by scanning electron microscopy. RESULTS: Silicone oil strongly adhered to holes and to the IOL surface especially in silicone and PMMA IOLs. Highly hydrophylic IOLs-like the heparin-surface-modified and hydrogel IOL-cleared from silicone oil relatively early. This effect was more pronounced in the group with lipid-/serum solution than without. In some silicone IOLs silicone oil was strongly adherent to the lens and it was nearly impossible to wash off the oil even when using an alcoholic solution. One silicone IOL lost its haptics in the serum-oil-IOL-mixture, another lost small particles from the IOL surface. CONCLUSION: Silicone oil is more adherent to hydrophobic IOLs than to hydrophylic IOLs. Lipoproteins of the serum play an important role in facilitating an effect of silicone oil on IOL materials. We recommend highly hydrophylic especially surface-modified IOLs for lens implantation following vitreoretinal silicone oil surgery. Implantation of silicone IOLs in vitreoretinal high risk eyes should be avoided.

Equipment Failure Analysis↗

Histologic and histomorphometric analysis of three types of dental implants following 18 months of occlusal loading: a preliminary study in baboons.

The purpose of this study was to determine the percentage of 'bone area' (BA) and 'bone-to-implant contact' (BIC) of dental implants with different designs and surface modifications after functional loading. Three types of dental implants with fixed partial dentures were placed in the posterior jaws of adult baboons (commercially pure titanium (CpTi) screws, grit-blasted acid-etched (GBAE) screws, and titanium plasma-sprayed (TPS) cylinders), three of the same design per quadrant. After 18 months of functional loading, all implants investigated were successfully integrated in the jawbone and histologic and histomorphometric analyses were carried out. Statistical evaluation was performed with a mixed model with data given as least-square means and standard errors of the mean (SEM). Histologically, direct BIC without connective tissue interposed between implant surfaces and peri-implant bone was seen. Analysis of BA within 1 mm around implants showed significant differences between CpTi (50.5%) and TPS (39.7%) (+/-2.72 SEM; P<0.01) in the maxilla. To account for the different implant designs, absolute BIC was calculated. Significant differences were found between CpTi (23.9 mm) and TPS (15.1 mm) and between GBAE (27.2 mm) and TPS (15.1 mm) (+/-1.05 SEM; P<0.01) in the maxilla and between GBAE (26.5 mm) and TPS (19.6 mm) (+/-1.42 SEM; P<0.01) in the mandible. Overall, the data indicate that, in the maxilla, screw-shaped implants showed more absolute BIC than cylindrical implants, which had less maxillary than mandibular absolute BIC after 18 months of functional loading.

Acid Etching, Dental↗

Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis.

Dialysis membranes made from regenerated cellulose are under dispute because of their alleged lack of hemocompatibility. The introduction of membranes from synthetically modified cellulose, like cellulose acetate or Hemophan, has proven, however, that hemocompatible membranes can be fabricated from cellulose by means of chemical surface modifications. In addition to membranes made from modified cellulose like ethers or esters, which were investigated in earlier experiments, we looked for further cellulose modifications to be assessed for their hemocompatibility. For this purpose, we synthesized a series of cellulose carbamate derivatives to profit from the excellent hemocompatibility pattern of the urethane family. In vitro investigations on membranes made from these cellulose modifications proved a direct relationship between the degree of modification and hemocompatibility. This was proven for the following 3 representative hemocompatibility parameters: complement C5a generation, thrombin-antithrombin (TAT) III formation, and platelet count (PC). As already shown for modifications made from cellulose esters, a direct dependency between improved hemocompatibility and the degree of substitution (DS) in the cellulose molecule could be found. In our experiments, a degree of substitution below a value of 0.1 led to a nearly complete suppression of complement activation for all cellulose carbamates under investigation. In contrast to data on cellulose esters, we observed that molecular weight or molecular conformation of chemical substituents exerted only a minor effect on the hemocompatibility pattern. In addition, data on cellulose carbamate esters (e.g., cellulose succinate-phenyl-carbamate) show that a simultaneous but balanced substitution with hydrophilic and hydrophobic groups at the surface of the cellulose polymer is a further prerequisite for optimal hemocompatibility. It seems that the carbamate configuration per se has a positive effect on the hemocompatibility pattern of synthetically modified cellulose membranes.

Antithrombin III↗

Adsorption of mycotoxins by organozeolites.

Adsorption of zearalenone (ZEN), ochratoxin A (OCHRA) and aflatoxin B1 (AFB1) on natural zeolite, clinoptilolite, modified with different amounts of octadecyldimethylbenzyl ammonium (ODMBA) ions was investigated. Results showed that adsorption of hydrophobic ionizable ZEN on unmodified zeolite tuff was very low and that adsorption on organozeolites increased with increasing hydrophobicity of the zeolitic surface. The adsorption was independent of the form of ZEN in solution and the solution pH, indicating that hydrophobic interactions with ODMBA are responsible for ZEN adsorption. Adsorption of low polar ionizable OCHRA on organozeolites also increased with increasing hydrophobicity of the zeolitic surface, however, OCHRA showed moderate adsorption on unmodified zeolitic tuff at pH 3. OCHRA adsorption on unmodified zeolite as well as on lower surface coverage of organozeolite was dependent on the form of OCHRA in solution; there was a decrease of adsorption at high pH, where OCHRA is in the anionic form. It indicated that at acidic pH, low surface coverage allows some combination of hydrophobic interaction with ODMBA and interactions with the surface of the zeolite. At higher surface coverage, the OCHRA adsorption was higher and practically independent of pH, indicating that the hydrophobic interactions of OCHRA with ODMBA are responsible for its adsorption. Nonionizable low polar AFB1 had a high affinity for the unmodified zeolitic tuff and the adsorption of AFB1 was greatly reduced for organozeolites, indicating that AFB1 does not have high tendency for hydrophobic interactions with ODMBA. pH dependence of AFB1 adsorption, while AFB1 has the same form at all pHs, demonstrated that the surface modification of the zeolite depends on pH and that these modifications have influence on its adsorption. The calculated dipole moments of neutral mycotoxin molecules: AFB1-9.5D, OCHRA-6.9D and ZEN-2.2D are in qualitative agreement with adsorption experimental data.

Adsorption↗

The human bone-oxidized titanium implant interface: A light microscopic, scanning electron microscopic, back-scatter scanning electron microscopic, and energy-dispersive x-ray study of clinically retrieved dental implants.

BACKGROUND: Surface modification of titanium implants by anodic oxidation may lead to enhanced bone integration. For instance, in vivo studies have demonstrated formation of more bone contacts in less time than for turned control implants. In addition, oxidized implants have shown a higher resistance to torque forces, indicating a strong interlock between bone and the oxide layer. However, the structure of the oxidized titanium-bone interface in high resolution is not known. PURPOSE: The aim of the study was to analyze the human bone-oxidized titanium interface at a high-resolution level. Of particular interest was the relationship between bone tissue and the pores of the surface oxide. MATERIALS AND METHODS: Twelve clinically retrieved implants with an oxidized surface (TiUnite, Nobel Biocare AB, Göteborg, Sweden) were used. Seven were regular dental implants and five were experimental mini-implants and had been subjected to immediate, early, or no loading. They were retrieved after 5 to 9 months of healing and were processed and analyzed using light microscopy, scanning electron microscopy (SEM) in normal and back-scatter (BS-SEM) modes, and energy-dispersive x-ray (EDX) analysis techniques. RESULTS: Bone formation was observed to occur from adjacent bone structures toward the implant surface, and it was evident that bone formation had occurred at the implant surface. SEM, BS-SEM, and EDX revealed that mineralized bone had grown into the pores of the surface oxide layer, including pores with small diameters (< 2 microm). CONCLUSIONS: The clinically retrieved oxidized implants showed evidence of bone growth into the pores of the surface oxide layer. The findings indicate the establishment of a strong interlock between the bone and the oxidized titanium implant, which is suggested to be beneficial for clinical performance.

Coated Materials, Biocompatible↗

Adhesion of adhesive resin to dental precious metal alloys. Part I. New precious metal alloys with base metals for resin bonding.

New dental precious metal alloys for resin bonding without alloy surface modification were developed by adding base metals (In, Zn, or Sn). Before this, binary alloys of Au, Ag, Cu, or Pd containing In, Zn, or Sn were studied for water durability and bonding strength with 4-META resin. The adhesion ability of the binary alloys was improved by adding In equivalent to 15% of Au content, Zn equivalent to 20% of Ag content, and In, Zn, or Sn equivalent to 5% of Cu content. There was no addition effect of the base metals on Pd, however 15% of In addition improved adhesion with Pd-based alloys containing equi-atomic % of Cu and Pd. The alloy surfaces were analyzed by XPS and showed that oxides such as In2O3, ZnO, or SnO play an important role in improving the adhesive ability of the alloys.

Acrylic Resins↗

Modification of the surface electronic and chemical properties of Pt(111) by subsurface 3d transition metals.

The modification of the electronic and chemical properties of Pt(111) surfaces by subsurface 3d transition metals was studied using density-functional theory. In each case investigated, the Pt surface d-band was broadened and lowered in energy by interactions with the subsurface 3d metals, resulting in weaker dissociative adsorption energies of hydrogen and oxygen on these surfaces. The magnitude of the decrease in adsorption energy was largest for the early 3d transition metals and smallest for the late 3d transition metals. In some cases, dissociative adsorption was calculated to be endothermic. The surfaces investigated in this study had no lateral strain in them, demonstrating that strain is not a necessary factor in the modification of bimetallic surface properties. The implications of these findings are discussed in the context of catalyst design, particularly for fuel cell electrocatalysts.

Journal Article↗

Transplantation of human endothelial cell monolayer on artificial vascular prosthesis: the effect of growth-support surface chemistry, cell seeding density, ECM protein coating, and growth factors.

The failure rates of synthetic vascular grafts, when placed in low blood flow environments in humans, are not acceptable. Thus, endothelial cell (EC) seeding technology of vascular grafts was developed to prepare prostheses lined with a human monolayer expressing optimal thromboresistant properties. In a clinical setting, endothelialization of a graft can be achieved using higher cell seeding densities, or by creating a surface on which EC can adhere and grow to confluence. But, human endothelial cells show little or no proliferation on the currently available graft materials. In this study, surface modification of PTFE and ePTFE by ammonia plasma treatment was carried out to enhance its interactions with ECM protein, EC growth factors, and with EC harvested from human umbilical vein (HUVEC), and from human saphenous veins (HSVEC). Our data shows that various vascular graft materials generated from ammonia plasma treated PTFE and ePTFE exhibited statistically significant improvements in HUVEC and HSVEC growth when compared to their respective controls (p values < 0.001). Growth of HSVEC on ammonia plasma treated ePTFE without ECM protein coating was also found to be statistically significant in comparison to that on fibronectin coated ePTFE (p < 0.001). The final HSVEC cell densities found on various ePTFE surfaces prepared from ammonia plasma treated ePTFE, suggests that transplantation of HSVEC monolayers on vascular prostheses can be established within clinically relevant times. Ammonia plasma treatment process provides an unique opportunity to surface modify prosthetic materials of various construct to transplant mammalian cells including those that have undergone ex vivo gene transfer, and to deliver angiogenic molecules to a target area for tissue development.

Blood Vessel Prosthesis↗

Carboxylic acid-functionalized conductive polypyrrole as a bioactive platform for cell adhesion.

Electroactive polymers such as polypyrrole (PPy) are highly attractive for a number of biomedical applications, including their use as coatings for electrodes or neural probes and as scaffolds to induce tissue regeneration. Surface modification of these materials with biological moieties is desired to enhance the biomaterial-tissue interface and to promote desired tissue responses. Here, we present the synthesis and physicochemical characterization of poly(1-(2-carboxyethyl)pyrrole) (PPyCOOH), a PPy derivative that contains a chemical group that can be easily modified with biological moieties at the N-position of the polymer backbone. FTIR, XPS, and fluorescence microscopy were used to demonstrate the successful incorporation of carboxylic acid (-COOH) functionality into PPy materials, and a four-point probe analysis was used to demonstrate electrical conductivity in the semiconductor range. Human umbilical vascular endothelial cells (HUVECs) cultured on PPyCOOH films surface-modified with the cell-adhesive Arg-Gly-Asp (RGD) motif demonstrated improved attachment and spreading. Thus, PPyCOOH could be useful in developing PPy composites that contain a variety of biological molecules as bioactive conducting platforms for specific biomedical purposes.

Carboxylic Acids↗

CD4+ T cells and toll-like receptors recognize Salmonella antigens expressed in bacterial surface organelles.

A better understanding of immunity to infection is revealed from the characteristics of microbial ligands recognized by host immune responses. Murine infection with the intracellular bacterium Salmonella generates CD4+ T cells that specifically recognize Salmonella proteins expressed in bacterial surface organelles such as flagella and membrane vesicles. These natural Salmonella antigens are also ligands for Toll-like receptors (TLRs) or avidly associated with TLR ligands such as lipopolysaccharide (LPS). PhoP/PhoQ, a regulon controlling Salmonella virulence and remodeling of LPS to resist innate immunity, coordinately represses production of surface-exposed antigens recognized by CD4+ T cells and TLRs. These data suggest that genetically coordinated surface modifications may provide a growth advantage for Salmonella in host tissues by limiting both innate and adaptive immune recognition.

Animals↗